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Neurology Today:
doi: 10.1097/01.NT.0000369625.43305.9a
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OXYTOCIN FOUND TO PROMOTE SOCIAL BEHAVIOR IN ASPERGER SYNDROME

TALAN, JAMIE

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ARTICLE IN BRIEF

Investigators reported that Asperger syndrome patients who were given oxytocin intranasally showed improved social behavior in an experiment involving a computer simulation of a game of toss.

Oxytocin, a hormone that has been shown to bind mother to child, seems to help people with Asperger syndrome gain a social edge, according to a report that appeared online Feb. 16 in the Proceedings of the National Academy of Sciences. The finding suggests that their brains may have the hardware in place to form closer social connections but the software (in this case a chemical) may be in short supply.

Oxytocin is secreted by the pituitary gland at the base of the brain, stimulating uterine contractions and the flow of milk. The hormone flows to the brain's amygdala and the hypothalamus sections, suggesting these are the areas involved in mediating mothering behaviors like caring, cuddling, and protecting.

A team of French researchers led by Angela Sirigu, PhD, of the Institute of Cognitive Science at the Centre National de la Recherde Scientifique [National Center for Scientific Research], tested whether oxytocin given intranasally to people with Asperger syndrome during a simulated game of catch would promote more social behavior. The more times a person on the screen threw the ball to the patient — and the patient threw it back – the stronger the social interaction. The exchange with the computer character that they felt more connection with – getting and receiving more balls — sparked enhanced social cooperation and a feeling of trust and preference. The researchers said the finding reflects an ability to bond socially, something that seems to be a weak skill in patients with Asperger syndrome.

“Individuals suffering from high-functioning autism spectrum disorders are impaired in understanding social cues and in responding to them,” the French team wrote.

Dr. Sirigu and her colleagues recruited 13 people with Asperger syndrome who have intact language but have difficulty navigating the social milieu of everyday life. “They show specific impairments in understanding the intentions of others and lack of fast intuitive judgments about social contexts,” Dr. Sirigu said.

They wanted to determine whether oxytocin would alter their behavior. Other animal studies had suggested that the hormone is involved in lactation, mother-infant attachments, grooming, approach behavior, and other social exchanges. Studies with normal volunteers suggested that a nasal dose of oxytocin triggered more feelings of trust towards another person.

Figure. DR. ANGELA S...
Figure. DR. ANGELA S...
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STUDY PROTOCOLS, RESULTS

During the study, the patients participated in an interactive computer simulation involving a multi-round ball toss. They threw the ball back and forth with three fictional partners. The program was designed so that one of the characters threw more balls to the patient, one avoided throwing to the patient, and one was more neutral. Investigators compared the reaction of the patients and 13 of healthy volunteers before and after exposure to oxytocin. They also recorded eye movements during another task where the study subjects were asked to look at a series of faces.

The team measured oxytocin levels in blood samples taken in patients and volunteers. In patients, oxytocin was measured before and after the administration of the hormone. The oxytocin levels were lower in the patients (1.09pg/mL) than in controls (7.28pg/mL). After the patients received 240 IUs of oxytocin intranasally, they showed an increase in plasma oxytocin concentrations. The patient levels never reached the normal concentrations seen in healthy volunteers.

Before the patient received oxytocin they were not able to discriminate between the different cooperative styles of the three fictional characters. The healthy control group could. After receiving oxytocin, the patients were able to understand and seemed to care (based on ratings done after the experiment) that one character was throwing more balls his or her way. They reported feeling trust and a preference to cooperate more with the character. The first study also included a money reward for completing the task. They performed a second study without the money reward to see if it confounded the original results. It didn't.

In the study where they measured eye movements the study subjects were asked to look at individual faces and say whether the face was male or female and to determine the gaze of the face. During the task the researchers recorded the eye movements of the patients and the normal volunteers.

Figure. DR. THOMAS R...
Figure. DR. THOMAS R...
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According to Dr. Sirigu, oxytocin modified the patient's responses to the faces. Those taking oxytocin spent more time staring at the faces, although even exposure to the hormone didn't bring their gaze time up to those of the normal volunteers.

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EXPERT COMMENTARY

Figure. DR. NANCY J....
Figure. DR. NANCY J....
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Independent experts who study autism said the hormone's association with improving social behavior was important, but questioned whether this one lone hormone is at the heart of Asperger syndrome.

Thomas Insel, MD, director of the National Institute of Mental Health, and a leading expert on oxytocin's role in social affiliation, said that the study is “one more piece of evidence that oxytocin increases social behavior, building on studies of healthy volunteers” — and prairie voles.

Dr. Insel studied the Midwestern voles during his tenure as director of the Yerkes Primate Laboratory in Atlanta, GA, and discovered that two hormones – oxytocin for females and vasopressin for males — were determining whether the voles mate for life or not. Both species had similar levels of the hormones but it was the location of the hormones that set the stage for bonding. The limbic region of the brain is generally rich in oxytocin in the prairie vole, but the loner vole is virtually bereft of the chemical — except while the mother cares for her newborn pups, Dr. Insel said.

Many labs have since speculated about oxytocin's role in triggering autism. There is some evidence from genetic studies that it may not be working properly in some people with the disorder. But the nature of the hormone does not make it a suitable treatment, even if it does show some acute benefits, Dr. Insel said.

“The hormone has a short half-life and its penetration into the brain after nasal administration is variable,” he added. “But an orally active, non-peptide drug that activates brain oxytocin receptors could be a useful treatment for the social deficits in autism.” He said that Pfizer is developing an oxytocin-like drug but it would be years before such large scale studies could be carried out to see if these medications could help reduce some of the symptoms of autism, Dr. Insel added.

Nancy J. Minshew, MD, professor of psychiatry and neurology at the University of Pittsburgh School of Medicine, and director of its Autism Center of Excellence, agreed that the findings were interesting, but took issue with the focus on treating social bonding. “I don't think oxytocin plays a central role in the cause of autism. This hormone, or rather the gene that makes it, may modify or contribute to the variability in the ASD [autism spectrum disorder] phenotype. To me the evidence indicates that autism results from abnormalities in the development of the ‘hardwiring’ that is, the circuitry of the brain, not in neurotransmitter or neuroendocrine levels.”

Dr. Minshew's work has focused on understanding the cognitive, neurologic, brain and genetic mechanisms that underlie autism. She believes that these conditions affect the development of the distributed brain circuitry that supports abilities in the cognitive and language domains as much as social abilities; it also affects motor, sensory, balance, mood, temperament and emotion domains. Hence, she contends that ASDs cannot be reduced to disorders of social affiliation or motivation.

Dr. Minshew added that a leader in the field of autism research Sir Michael Rutter, a professor of developmental psychopathology at the Institute of Psychiatry of King's College London, remarked at a 2008 conference that ASDs were notable for their unresponsiveness to psychotropic medications.

“To me that was another way of saying ASDs are not caused by neurotransmitters or other humoral factors, nor would they be fixed by those,” said Dr. Minshew. “They are the result of altered hard wiring.”

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REFERENCES

• Andari E, Duhamel JR, Sirigue A, et al. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A 2010; E-pub 2010 Feb. 16.

• TR Insel. Oxytocin—a neuropeptide for affiliation: evidence from behavioral, receptor. Psychoneuroendocrinology 1992; 17(1):3–35.

• Insel TR, Shapiro LE. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc Natl Acad Sci U S A 1992;89(13):5981–5985.

• Kosfeld M, Heinrichs M, Fehr E, et al: Oxytocin increases trust in humans. Nature 2005; 435(7042):674–676.

• S Jacob, Brune CW, Cook EH Jr, et al: Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 2007;417(1):6–9.

©2010 American Academy of Neurology

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